ResearchPad - pain-medicine https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Measuring problem prescription opioid use among patients receiving long-term opioid analgesic treatment: development and evaluation of an algorithm for use in EHR and claims data]]> https://www.researchpad.co/article/elastic_article_15181 Opioid surveillance in response to the opioid epidemic will benefit from scalable, automated algorithms for identifying patients with clinically documented signs of problem prescription opioid use. Existing algorithms lack accuracy. We sought to develop a high-sensitivity, high-specificity classification algorithm based on widely available structured health data to identify patients receiving chronic extended-release/long-acting (ER/LA) therapy with evidence of problem use to support subsequent epidemiologic investigations.Methods Outpatient medical records of a probability sample of 2,000 Kaiser Permanente Washington patients receiving ≥60 days’ supply of ER/LA opioids in a 90-day period from 1 January 2006 to 30 June 2015 were manually reviewed to determine the presence of clinically documented signs of problem use and used as a reference standard for algorithm development. Using 1,400 patients as training data, we constructed candidate predictors from demographic, enrollment, encounter, diagnosis, procedure, and medication data extracted from medical claims records or the equivalent from electronic health record (EHR) systems, and we used adaptive least absolute shrinkage and selection operator (LASSO) regression to develop a model. We evaluated this model in a comparable 600-patient validation set. We compared this model to ICD-9 diagnostic codes for opioid abuse, dependence, and poisoning. This study was registered with ClinicalTrials.gov as study NCT02667262 on 28 January 2016.Results We operationalized 1,126 potential predictors characterizing patient demographics, procedures, diagnoses, timing, dose, and location of medication dispensing. The final model incorporating 53 predictors had a sensitivity of 0.582 at positive predictive value (PPV) of 0.572. ICD-9 codes for opioid abuse, dependence, and poisoning had a sensitivity of 0.390 at PPV of 0.599 in the same cohort.Conclusions Scalable methods using widely available structured EHR/claims data to accurately identify problem opioid use among patients receiving long-term ER/LA therapy were unsuccessful. This approach may be useful for identifying patients needing clinical evaluation. ]]> <![CDATA[External Validation of a Pharmacokinetic Model of Propofol for Target-Controlled Infusion in Children under Two Years Old]]> https://www.researchpad.co/article/N68561e64-fa5c-4151-a006-f95e88088bd6

Background

Previously, a linked pharmacokinetic-pharmacodynamic model (the Kim model) of propofol with concurrent infusion of remifentanil was developed for children aged 2–12 years. There are few options for pharmacokinetic-pharmacodynamic model of propofol for children under two years old. We performed an external validation of the Kim model for children under two years old to evaluate whether the model is applicable to this age group.

Methods

Twenty-four children were enrolled. After routine anesthetic induction, a continuous infusion of 2% propofol and remifentanil was commenced using the Kim model. The target effect-site concentration of propofol was set as 2, 3, 4, and 5 μg/mL, followed by arterial blood sampling after 10 min of each equilibrium. Population estimates of four parameters—pooled bias, inaccuracy, divergence, and wobble—were used to evaluate the performance of the Kim model.

Results

A total of 95 plasma concentrations were used for evaluation of the Kim model. The population estimate (95% confidence interval) of bias was −0.96% (−8.45%, 6.54%) and that of inaccuracy was 21.0% (15.0%–27.0%) for the plasma concentration of propofol.

Conclusion

The pooled bias and inaccuracy of the pharmacokinetic predictions are clinically acceptable. Therefore, our external validation of the Kim model indicated that the model can be applicable to target-controlled infusion of propofol in children younger than 2 years, with the recommended use of actual bispectral index monitoring in clinical settings that remifentanil is present.

Trial Registration

Clinical Research Information Service Identifier: KCT0001752

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<![CDATA[Management of pain in patients with temporomandibular disorder (TMD): challenges and solutions]]> https://www.researchpad.co/article/5bfb30d6d5eed0c48496381b

Thanks to advances in neuroscience, biopsychosocial models for diagnostics and treatment (including physical, psychological, and pharmacological therapies) currently have more clinical support and scientific growth. At present, a conservative treatment approach prevails over surgery, given it is less aggressive and usually results in satisfactory clinical outcomes in mild–moderate temporomandibular disorder (TMD). The aim of this review is to evaluate the recent evidence, identify challenges, and propose solutions from a clinical point of view for patients with craniofacial pain and TMD. The treatment we propose is structured in a multi-modal approach based on a biobehavioral approach that includes medical, physiotherapeutic, psychological, and dental treatments. We also propose a new biobehavioral model regarding pain perception and motor behavior for the diagnosis and treatment of patients with painful TMD.

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<![CDATA[Blinatumomab retreatment after relapse in patients with relapsed/refractory B-precursor acute lymphoblastic leukemia]]> https://www.researchpad.co/article/5b4ad4a6463d7e6c275999f9 ]]> <![CDATA[Local anesthetics for brain tumor resection: current perspectives]]> https://www.researchpad.co/article/5b4ac456463d7e6b46cb191c

This review summarizes the added value of local anesthetics in patients undergoing craniotomy for brain tumor resection, which is a procedure that is carried out frequently in neurosurgical practice. The procedure can be carried out under general anesthesia, sedation with local anesthesia or under local anesthesia only. Literature shows a large variation in the postoperative pain intensity ranging from no postoperative analgesia requirement in two-thirds of the patients up to a rate of 96% of the patients suffering from severe postoperative pain. The only identified causative factor predicting higher postoperative pain scores is infratentorial surgery. Postoperative analgesia can be achieved with multimodal pain management where local anesthesia is associated with lower postoperative pain intensity, reduction in opioid requirement and prevention of development of chronic pain. In awake craniotomy patients, sufficient local anesthesia is a cornerstone of the procedure. An awake craniotomy and brain tumor resection can be carried out completely under local anesthesia only. However, the use of sedative drugs is common to improve patient comfort during craniotomy and closure. Local anesthesia for craniotomy can be performed by directly blocking the six different nerves that provide the sensory innervation of the scalp, or by local infiltration of the surgical site and the placement of the pins of the Mayfield clamp. Direct nerve block has potential complications and pitfalls and is technically more challenging, but mostly requires lower total doses of the local anesthetics than the doses required in surgical-site infiltration. Due to a lack of comparative studies, there is no evidence showing superiority of one technique versus the other. Besides the use of other local anesthetics for analgesia, intravenous lidocaine administration has proven to be a safe and effective method in the prevention of coughing during emergence from general anesthesia and extubation, which is especially appreciated after brain tumor resection.

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<![CDATA[Effect of bupivacaine and adjuvant drugs for regional anesthesia on nerve tissue oximetry and nerve blood flow]]> https://www.researchpad.co/article/5b4a8233463d7e6681b4b2fc

Background

Nerve blood flow has a critical role in acute and chronic pathologies in peripheral nerves. Influences of local anesthetics and adjuvants on tissue perfusion and oxygenation are deemed as relevant factors for nerve damage after peripheral regional anesthesia. The link between low tissue perfusion due to local anesthetics and resulting tissue oxygenation is unclear.

Methods

Combined tissue spectrophotometry and laser-Doppler flowmetry were used to assess nerve blood flow in 40 surgically exposed median nerves in pigs, as well as nerve tissue oximetry for 60 min. After baseline measurements, test solutions saline (S), bupivacaine (Bupi), bupivacaine with epinephrine (BupiEpi), and bupivacaine with clonidine (BupiCloni) were applied topically.

Results

Bupivacaine resulted in significant decrease in nerve blood flow, as well as tissue oximetry values, compared with saline control. Addition of epinephrine resulted in a rapid, but nonsignificant, reduction of nerve blood flow and extensive lowering of tissue oximetry levels. The use of clonidine resulted in a reduction of nerve blood flow, comparable to bupivacaine alone (relative blood flow at T60 min compared with baseline, S: 0.86 (0.67–1.18), median (25th–75th percentile); Bupi: 0.33 (0.25–0.60); BupiCloni: 0.43 (0.38–0.63); and BupiEpi: 0.41(0.30–0.54). The use of adjuvants did not result in any relevant impairment of tissue oximetry values (saturation values in percent at T60, S: 91.5 [84–95]; Bupi: 76 [61–86]; BupiCloni: 84.5 [76–91]; and BupiEpi: 91 [56–92]).

Conclusion

The application of bupivacaine results in lower nerve blood flow, but does not induce relevant ischemia. Despite significant reductions in nerve blood flow, the addition of clonidine or epinephrine to bupivacaine had no significant impact on nerve tissue oximetry compared with bupivacaine alone. Nerve ischemia due to local anesthetics is not enhanced by the adjuvants clonidine or epinephrine.

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<![CDATA[Headache following head injury: a population-based longitudinal cohort study (HUNT)]]> https://www.researchpad.co/article/5b4a49e6463d7e44fe5eb45b

Background

Headache is the most frequent symptom following head injury, but long-term follow-up of headache after head injury entails methodological challenges. In a population-based cohort study, we explored whether subjects hospitalized due to a head injury more often developed a new headache or experienced exacerbation of previously reported headache compared to the surrounding population.

Methods

This population-based historical cohort study included headache data from two large epidemiological surveys performed with an 11-year interval. This was linked with data from hospital records on exposure to head injury occurring between the health surveys. Participants in the surveys who had not been hospitalized because of a head injury comprised the control group. The head injuries were classified according to the Head Injury Severity Scale (HISS). Multinomial logistic regression was performed to investigate the association between head injury and new headache or exacerbation of pre-existing headache in a population with known pre-injury headache status, controlling for potential confounders.

Results

The exposed group consisted of 294 individuals and the control group of 25,662 individuals. In multivariate analyses, adjusting for age, sex, anxiety, depression, education level, smoking and alcohol use, mild head injury increased the risk of new onset headache suffering (OR 1.74, 95% CI 1.05–2.87), stable headache suffering (OR 1.70, 95% CI 1.15–2.50) and exacerbation of previously reported headache (OR 1.93, 95% CI 1.24–3.02). The reference category was participants without headache in both surveys.

Conclusion

Individuals hospitalized due to a head injury were more likely to have new onset and worsening of pre-existing headache and persistent headache, compared to the surrounding general population. The results support the entity of the ICHD-3 beta diagnosis “persistent headache attributed to traumatic injury to the head”.

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<![CDATA[New model of vincristine-induced neuropathic pain in children: a first step towards prediction and prevention]]> https://www.researchpad.co/article/5bf49226d5eed0c484763ad0 ]]> <![CDATA[Cebranopadol, a novel first-in-class analgesic drug candidate: first experience in patients with chronic low back pain in a randomized clinical trial]]> https://www.researchpad.co/article/5bf4922bd5eed0c484763b7f

Supplemental Digital Content is Available in the Text.

Cebranopadol, a novel first-in-class combination of nociceptin/orphanin FQ and opioid peptide receptor agonism, as a potential treatment for moderate to severe chronic low back pain.

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<![CDATA[miR-34c-5p functions as pronociceptive microRNA in cancer pain by targeting Cav2.3 containing calcium channels]]> https://www.researchpad.co/article/5bf4922ad5eed0c484763b2a

Supplemental Digital Content is Available in the Text.

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<![CDATA[Safety and efficacy of neublastin in painful lumbosacral radiculopathy: a randomized, double-blinded, placebo-controlled phase 2 trial using Bayesian adaptive design (the SPRINT trial)]]> https://www.researchpad.co/article/5bf49228d5eed0c484763afb

Supplemental Digital Content is Available in the Text.

Neublastin showed some evidence of pain relief among patients with painful lumbosacral radiculopathy; however, there was no clear dose–response relationship.

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<![CDATA[PKM2 is involved in neuropathic pain by regulating ERK and STAT3 activation in rat spinal cord]]> https://www.researchpad.co/article/5b4a0487463d7e3e66f5dd72

Background

Pyruvate kinase isozymes M2 (PKM2), as a member of pyruvate kinase family, plays a role of glycolytic enzyme in glucose metabolism. It also functions as protein kinase in cell proliferation, signaling, immunity, and gene transcription. In this study, the role of PKM2 in neuropathic pain induced by chronic constriction injury (CCI) was investigated.

Methods

Rats were randomly grouped to establish CCI models. PKM2, extracellular regulated protein kinases (EKR), p-ERK, signal transducers and activators of transcription (STAT3), p-STAT3, phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) and p-PI3K/AKT proteins expression in spinal cord was examined by Western blot analysis. Cellular location of PKM2 was examined by immunofluorescence. Knockdown of PKM2 was achieved by intrathecal injection of specific small interfering RNA (siRNA). Von Frey filaments and radiant heat tests were performed to determine mechanical allodynia and thermal hyperalgesia respectively. Lactate and adenosine triphosphate (ATP) contents were measured by specific kits. Tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β) levels were detected by ELISA kits.

Results

CCI markedly increased PKM2 level in rat spinal cord. Double immunofluorescent staining showed that PKM2 co-localized with neuron, astrocyte, and microglia. Intrathecal injection of PKM2 siRNA not only attenuated CCI-induced ERK and STAT3 activation, but also attenuated mechanical allodynia and thermal hyperalgesia induced by CCI. However, PKM2 siRNA failed to inhibit the activation of AKT. In addition, PKM2 siRNA significantly suppressed the production of lactate and pro-inflammatory mediators.

Conclusion

Our findings demonstrate that inhibiting PKM2 expression effectively attenuates CCI-induced neuropathic pain and inflammatory responses in rats, possibly through regulating ERK and STAT3 signaling pathway.

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<![CDATA[Clinical signs and electroencephalographic patterns of emergence from sevoflurane anaesthesia in children]]> https://www.researchpad.co/article/5bf1b09ed5eed0c484d286db <![CDATA[Elevated Production of Nociceptive CC Chemokines and sE-Selectin in Patients With Low Back Pain and the Effects of Spinal Manipulation]]> https://www.researchpad.co/article/5bf1b0a5d5eed0c484d2880d <![CDATA[Patients With Knee Osteoarthritis Who Score Highly on the PainDETECT Questionnaire Present With Multimodality Hyperalgesia, Increased Pain, and Impaired Physical Function]]> https://www.researchpad.co/article/5bf1b0a3d5eed0c484d287a5 <![CDATA[Sensory phenotype and risk factors for painful diabetic neuropathy: a cross-sectional observational study]]> https://www.researchpad.co/article/5b45c189463d7e5426b74cd5

Supplemental Digital Content is Available in the Text.

Cross-sectional observational study in a cohort of 232 diabetic polyneuropathy patients confirmed higher severity of neuropathy and predominant loss-of-function sensory profile in painful cases.

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<![CDATA[Response to duloxetine in chronic low back pain: exploratory post hoc analysis of a Japanese Phase III randomized study]]> https://www.researchpad.co/article/5b432a46463d7e234194a95a

Purpose

Duloxetine is efficacious for chronic low back pain (CLBP). This post hoc analysis of a Japanese randomized, placebo-controlled trial (ClinicalTrials.gov, NCT01855919) assessed whether patients with CLBP with early pain reduction or treatment-related adverse events of special interest (TR-AESIs; nausea, somnolence, constipation) have enhanced responses to duloxetine.

Patients and methods

Patients (N = 456) with CLBP for ≥6 months and Brief Pain Inventory (BPI) average pain severity score of ≥4 were randomized (1:1) to duloxetine 60 mg/day or placebo for 14 weeks. Primary outcome was change from baseline in BPI average pain severity score (pain reduction). Subgroup analyses included early pain reduction (≥30%, 10%–30%, or <10% at Week 4) and early TR-AESIs (with or without TR-AESIs by Week 2). Measures included changes from baseline in BPI average pain severity score and BPI Interference scores (quality of life; QOL), and response rate (≥30% or ≥50% pain reduction at Week 14).

Results

Patients with ≥30% early pain reduction (n = 108) or early TR-AESIs (n = 50) had significantly greater improvements in pain and QOL than placebo-treated patients (n = 226), whereas patients with 10%–30% (n = 63) or <10% (n = 48) pain reduction did not; patients without early TR-AESIs (n = 180) had significant improvements in pain at Week 14. Response rates (≥30%/≥50% pain reduction) were 94.4%/82.4%, 66.7%/49.2%, and 25.0%/18.8% for patients with ≥30%, 10%–30%, and <10% early pain reduction, respectively, 74.0%/64.0% for patients with early TR-AESIs, 67.2%/54.4% for patients without early TR-AESIs, and 52.2%/39.4% for placebo.

Conclusion

Early pain reduction or TR-AESIs may predict which CLBP patients are most likely to respond to duloxetine with improvements in pain and QOL.

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<![CDATA[Epac–protein kinase C alpha signaling in purinergic P2X3R-mediated hyperalgesia after inflammation]]> https://www.researchpad.co/article/5bccad9840307c364ce7ade0 <![CDATA[Deficits in pain perception in borderline personality disorder: results from the thermal grill illusion]]> https://www.researchpad.co/article/5bcbfb6b40307c58a99fb39c <![CDATA[Dimethylarginine dimethylaminohydrolase 1 is involved in spinal nociceptive plasticity]]> https://www.researchpad.co/article/5bcbfb6640307c58a99fb39b