Perioperative mental health intervention for depression and anxiety symptoms in older adults study protocol: design and methods for three linked randomised controlled trials.

INTRODUCTION: Preoperative anxiety and depression symptoms among older surgical patients are associated with poor postoperative outcomes, yet evidence-based interventions for anxiety and depression have not been applied within this setting. We present a protocol for randomised controlled trials (RCTs) in three surgical cohorts: cardiac, oncological and orthopaedic, investigating whether a perioperative mental health intervention, with psychological and pharmacological components, reduces perioperative symptoms of depression and anxiety in older surgical patients. METHODS AND ANALYSIS: Adults ≥60 years undergoing cardiac, orthopaedic or oncological surgery will be enrolled in one of three-linked type 1 hybrid effectiveness/implementation RCTs that will be conducted in tandem with similar methods. In each trial, 100 participants will be randomised to a remotely delivered perioperative behavioural treatment incorporating principles of behavioural activation, compassion and care coordination, and medication optimisation, or enhanced usual care with mental health-related resources for this population. The primary outcome is change in depression and anxiety symptoms assessed with the Patient Health Questionnaire-Anxiety Depression Scale from baseline to 3 months post surgery. Other outcomes include quality of life, delirium, length of stay, falls, rehospitalisation, pain and implementation outcomes, including study and intervention reach, acceptability, feasibility and appropriateness, and patient experience with the intervention. ETHICS AND DISSEMINATION: The trials have received ethics approval from the Washington University School of Medicine Institutional Review Board. Informed consent is required for participation in the trials. The results will be submitted for publication in peer-reviewed journals, presented at clinical research conferences and disseminated via the Center for Perioperative Mental Health website. TRIAL REGISTRATION NUMBERS: NCT05575128, NCT05685511, NCT05697835, pre-results.

Cannabis oil extracts for chronic pain: what else can be learned from another structured prospective cohort?

Introduction: The use of medicinal cannabis for managing pain expands, although its efficacy and safety have not been fully established through randomized controlled trials. Objectives: This structured, prospective questionnaire-based cohort was aimed to assess long-term effectiveness and safety of cannabis oil extracts in patients with chronic pain. Methods: Adult Israeli patients licensed to use cannabis oil extracts for chronic pain were followed prospectively for 6 months. The primary outcome measure was change from baseline in average weekly pain intensity, and secondary outcomes were changes in related symptoms and quality of life, recorded before treatment initiation and 1, 3, and 6 months thereafter. Generalized linear mixed model was used to analyze changes over time. In addition, "responders" (≥30% reduction in weekly pain at any time point) were identified. Results: The study included 218 patients at baseline, and 188, 154, and 131 at 1, 3, and 6 months, respectively. At 6 months, the mean daily doses of cannabidiol and Δ9-tetrahydrocannabinol were 22.4 ± 24.0 mg and 20.8 ± 30.1 mg, respectively. Pain decreased from 7.9 ± 1.7 at baseline to 6.6 ± 2.2 at 6 months (F(3,450) = 26.22, P < 0.0001). Most secondary parameters also significantly improved. Of the 218 participants, 24% were "responders" but could not be identified by baseline parameters. "Responders" exhibited higher improvement in secondary outcomes. Adverse events were common but mostly nonserious. Conclusion: This prospective cohort demonstrated a modest overall long-term improvement in chronic pain and related symptoms and a reasonable safety profile with the use of relatively low doses of individually titrated Δ9-tetrahydrocannabinol and cannabidiol.

Perioperative Risk Factors for Persistent Postsurgical Pain After Inguinal Hernia Repair: Systematic Review and Meta-Analysis.

Persistent postsurgical pain (PPSP) is one of the most bothersome and disabling long-term complications after inguinal hernia repair surgery. Understanding perioperative risk factors that contribute to PPSP can help identify high-risk patients and develop risk-mitigation approaches. The objective of this study was to systematically review and meta-analyze risk factors that contribute to PPSP after inguinal hernia repair. The literature search resulted in 303 papers included in this review, 140 of which were used for meta-analyses. Our results suggest that younger age, female sex, preoperative pain, recurrent hernia, postoperative complications, and postoperative pain are associated with a higher risk of PPSP. Laparoscopic techniques reduce the PPSP occurrence compared to anterior techniques such as Lichtenstein repair, and tissue-suture techniques such as Shouldice repair. The use of fibrin glue for mesh fixation was consistently associated with lower PPSP rates compared to tacks, staples, and sutures. Considerable variability was observed with PPSP assessment and reporting methodology in terms of study design, follow-up timing, clarity of pain definition, as well as pain intensity or interference threshold. High or moderate risk of bias in at least one domain was noted in >75% of studies. These may limit the generalizability of our results. Future studies should assess and report comprehensive preoperative and perioperative risk factors for PPSP adjusted for confounding factors, and develop risk-prediction models to drive stratified PPSP-mitigation trials and personalized clinical decision-making. PERSPECTIVE: This systematic review and meta-analysis summarizes the current evidence on risk factors for persistent pain after inguinal hernia repair. The findings can help identify patients at risk and test personalized risk-mitigation approaches to prevent pain. PROSPERO REGISTRATION: htttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=154663.

Brain-Hazardous Medications and Potential Subadequate Antidepressant Dosing in Older Surgical Patients Receiving Home Antidepressants: An Observational Study of a Large US Health System.

BACKGROUND: Older surgical patients with depression often experience poor postoperative outcomes. Poor outcomes may stem from brain-hazardous medications and subadequate antidepressant dosing. METHODS: This was a retrospective, observational cohort study covering the period between January 1, 2021 and December 31, 2021. Patients ≥60 years of age who underwent inpatient surgery and had an overnight stay at an integrated academic health care system comprising 14 hospitals were eligible. We analyzed the prevalence of home central nervous system (CNS)-active potentially inappropriate medication (PIM) and potential subadequate antidepressant dosing in older surgical patients receiving home antidepressants. Univariable and multivariable regression models were used to identify factors associated with home CNS-active PIM prescribing and potential subadequate antidepressant dosing. Additionally, outcomes were compared among patients receiving and not receiving CNS-active PIMs and patients receiving and not receiving subadequate antidepressant dosing. RESULTS: A total of 8031 patients were included in this study (47% female, mean age = 70 years) of whom 2087 (26%) were prescribed antidepressants. Roughly one-half (49%, 95% confidence interval [CI], 46.5-50.1) of patients receiving home antidepressants were also receiving ≥1 CNS-active PIM and 29% (95% CI, 27.0-29.3) were receiving a potential subadequate dose. Factors associated with an increased likelihood of receiving a home CNS-active PIM included female sex (adjusted odds ratio [aOR], 1.46), anxiety (aOR, 2.43), asthma or chronic obstructive pulmonary disease (aOR, 1.39), and serotonin-norepinephrine reuptake inhibitor use (aOR, 1.54). Patients aged ≥75 years (aOR, 1.57), black race (aOR, 1.48) and those with congestive heart failure (aOR, 1.33) were more likely to be prescribed a potential subadequate antidepressant dose. Patients receiving potential subadequate antidepressant doses were discharged home less often (64% vs 73%), had a longer hospital length of stay (9 days vs 7 days), and a higher mortality rate (18% vs 10%) compared to patients receiving adequate home antidepressant doses (P-value for all <0.01). No differences in these outcomes were found among patients receiving home antidepressants with or without CNS-active PIMs. CONCLUSIONS: Older surgical patients receiving antidepressants are frequently prescribed brain-hazardous medications and potentially subadequate antidepressant doses. Those receiving subadequate antidepressant doses may be at risk for worse postoperative outcomes compared to patients receiving adequate doses. The role of preoperative medication optimization to improve outcomes for older surgical patients should be evaluated.

A novel theta-controlled vibrotactile brain-computer interface to treat chronic pain: a pilot study.

Limitations in chronic pain therapies necessitate novel interventions that are effective, accessible, and safe. Brain-computer interfaces (BCIs) provide a promising modality for targeting neuropathology underlying chronic pain by converting recorded neural activity into perceivable outputs. Recent evidence suggests that increased frontal theta power (4-7 Hz) reflects pain relief from chronic and acute pain. Further studies have suggested that vibrotactile stimulation decreases pain intensity in experimental and clinical models. This longitudinal, non-randomized, open-label pilot study's objective was to reinforce frontal theta activity in six patients with chronic upper extremity pain using a novel vibrotactile neurofeedback BCI system. Patients increased their BCI performance, reflecting thought-driven control of neurofeedback, and showed a significant decrease in pain severity (1.29 ± 0.25 MAD, p = 0.03, q = 0.05) and pain interference (1.79 ± 1.10 MAD p = 0.03, q = 0.05) scores without any adverse events. Pain relief significantly correlated with frontal theta modulation. These findings highlight the potential of BCI-mediated cortico-sensory coupling of frontal theta with vibrotactile stimulation for alleviating chronic pain.

Cognitive flexibility training for chronic pain: a randomized clinical study.

Introduction: Previous studies suggest an association between cognitive flexibility and development of chronic pain after surgery. It is not known whether cognitive flexibility can be improved in patients with chronic pain. Objectives: This study tested whether a neurocognitive training program results in improved cognitive flexibility and pain in patients with chronic pain. Methods: We conducted a single-center, prospective, randomized study investigating 5-week daily neurocognitive training in patients with chronic pain. Participants (n = 145) were randomized into neurocognitive training or care as usual, and they completed assessments at baseline, posttreatment, and 3 months. The treatment group was asked to spend 35 minutes daily completing a program with tasks on cognitive flexibility, memory, attention, and speed. The primary outcome was performance on the neurocognitive performance test (NCPT). Secondary outcomes included levels of pain interference and severity. Results: At 5 weeks, the treatment group showed greater improvements on NCPT compared with the control group (d = 0.37); effect size was smaller at 3 months (d = 0.18). The treatment group reported lower pain severity at 5 weeks (d = 0.16) and 3 months (d = 0.39) than the control group, but pain interference was only lower at 3 months (d = 0.20). Conclusions: Outcomes suggest that using neurocognitive training to modify cognitive flexibility in patients with chronic pain may improve pain severity. This study provided effect size estimates to inform sample size calculations for randomized controlled trials to test the effectiveness of neurocognitive interventions for the prevention and treatment of chronic pain.

Patient engagement in designing, conducting, and disseminating clinical pain research: IMMPACT recommended considerations.

ABSTRACT: In the traditional clinical research model, patients are typically involved only as participants. However, there has been a shift in recent years highlighting the value and contributions that patients bring as members of the research team, across the clinical research lifecycle. It is becoming increasingly evident that to develop research that is both meaningful to people who have the targeted condition and is feasible, there are important benefits of involving patients in the planning, conduct, and dissemination of research from its earliest stages. In fact, research funders and regulatory agencies are now explicitly encouraging, and sometimes requiring, that patients are engaged as partners in research. Although this approach has become commonplace in some fields of clinical research, it remains the exception in clinical pain research. As such, the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials convened a meeting with patient partners and international representatives from academia, patient advocacy groups, government regulatory agencies, research funding organizations, academic journals, and the biopharmaceutical industry to develop consensus recommendations for advancing patient engagement in all stages of clinical pain research in an effective and purposeful manner. This article summarizes the results of this meeting and offers considerations for meaningful and authentic engagement of patient partners in clinical pain research, including recommendations for representation, timing, continuous engagement, measurement, reporting, and research dissemination.

A Perioperative Mental Health Intervention for Depressed and Anxious Older Surgical Patients: Results From a Feasibility Study.

OBJECTIVES: The perioperative period is challenging and stressful for older adults. Those with depression and/or anxiety have an increased risk of adverse surgical outcomes. We assessed the feasibility of a perioperative mental health intervention composed of medication optimization and a wellness program following principles of behavioral activation and care coordination for older surgical patients. METHODS: We included orthopedic, oncologic, and cardiac surgical patients aged 60 and older. Feasibility outcomes included study reach, the number of patients who agreed to participate out of the total eligible; and intervention reach, the number of patients who completed the intervention out of patients who agreed to participate. Intervention efficacy was assessed using the Patient Health Questionnaire for Anxiety and Depression (PHQ-ADS). Implementation potential and experiences were collected using patient surveys and qualitative interviews. Complementary caregiver feedback was also collected. RESULTS: Twenty-three out of 28 eligible older adults participated in this study (mean age 68.0 years, 65% women), achieving study reach of 82% and intervention reach of 83%. In qualitative interviews, patients (n = 15) and caregivers (complementary data, n = 5) described overwhelmingly positive experiences with both the intervention components and the interventionist, and reported improvement in managing depression and/or anxiety. Preliminary efficacy analysis indicated improvement in PHQ-ADS scores (F = 12.13, p <0.001). CONCLUSIONS: The study procedures were reported by participants as feasible and the perioperative mental health intervention to reduce anxiety and depression in older surgical patients showed strong implementation potential. Preliminary data suggest its efficacy for improving depression and/or anxiety symptoms. A randomized controlled trial assessing the intervention and implementation effectiveness is currently ongoing.

Personal factors and baseline function in patients undergoing non-operative management for chronic hip-related groin pain: a cross-sectional study.

Aim: Little is known about the relationship between personal factors and perception of hip-related function among patients with chronic hip-related groin pain (HRGP) seeking non-operative management. This analysis was performed to determine if depressive symptoms, central sensitisation, movement evoked pain (MEP), pressure hypersensitivity and activity level were associated with patients' perception of hip-related function, represented by the International Hip Outcome Tool (iHOT-33). Methods: This cross-sectional study used baseline data from a pilot randomised clinical trial. Participants had anterior hip symptoms for at least 3 of the past 12 months reproduced on examination. Depressive symptoms, central sensitisation and activity level were quantified with self-report questionnaires. MEP was assessed during step down and squat. Pain pressure threshold (PPT) was used to assess pressure hypersensitivity. Statistical analysis was performed to assess bivariate association between variables and independent association of variables with iHOT-33. Results: Data from 33 participants (aged 18-40 years) with HRGP were analysed. Greater depressive symptoms (rs=-0.48, p=0.005), higher MEP during step down (rs=-0.36, p=0.040) and squat (rs=-0.39, p=0.024), and greater central sensitisation (rs=-0.33, p=0.058) were associated with lower (worse) iHOT-33 scores. Greater depressive symptoms (ß=-0.47, 95% CI -0.76 to -0.17; p=0.003) and higher MEP during squat (ß=-0.38, 95% CI -0.68 to -0.08; p=0.014) accounted for 37% of variability in iHOT-33. After adjusting for depressive symptoms and MEP, PPT, central sensitisation symptoms and activity level were not associated iHOT-33. Conclusions: In patients with HRGP seeking non-operative management, greater depressive symptoms and MEP are independently associated with worse self-perceived hip function. Trial registration number: NCT03959319.

Comparison of Joint Mobilization and Movement Pattern Training for Patients With Hip-Related Groin Pain: A Pilot Randomized Clinical Trial.

OBJECTIVE: The objective of this study was to assess the feasibility of completing a randomized clinical trial (RCT) and examine the preliminary effects of 2 interventions for hip-related groin pain (HRGP). METHODS: In this pilot RCT, patients with HRGP, who were 18 to 40 years old, were randomized (1:1 ratio) to a joint mobilization (JtMob) group or a movement pattern training (MoveTrain) group. Both treatments included 10 supervised sessions and a home exercise program. The goal of JtMob was to reduce pain and improve mobility through peripherally and centrally mediated pain mechanisms. The key element was physical therapist-provided JtMob. The goal of MoveTrain was to reduce hip joint stresses by optimizing the biomechanics of patient-specific tasks. The key element was task-specific instruction to correct abnormal movement patterns displayed during tasks. Primary outcomes were related to future trial feasibility. The primary effectiveness outcome was the Hip Disability and Osteoarthritis Outcome Score. Examiners were blinded to group; patients and treatment providers were not. Data collected at baseline and immediately after treatment were analyzed with analysis of covariance using a generalized linear model in which change was the dependent variable and baseline was the covariate. The study was modified due to the coronavirus disease 2019 (COVID-19) pandemic. RESULTS: The COVID-19 pandemic affected participation; 127 patients were screened, 33 were randomized (18 to the JtMob group and 15 to the MoveTrain group), and 29 (88%) provided posttreatment data. Treatment session adherence was 85%, and home exercise program component adherence ranged from 71 to 86%. Both groups demonstrated significant mean within-group improvements of ≥5 points on Hip Disability and Osteoarthritis Outcome Score scales. There were no between-group differences in effectiveness outcomes. CONCLUSIONS: A large RCT to assess the effects of JtMob and MoveTrain for patients with HRGP may be feasible. Preliminary findings suggested that JtMob or MoveTrain may result in improvements in patient-reported pain and activity limitations. IMPACT: The COVID-19 pandemic interfered with participation, but a randomized controlled trial may be feasible. Modification may be needed if the trial is completed during future pandemics.

An LC-ESI-MS/MS method for determination of ondansetron in low-volume plasma and cerebrospinal fluid: Method development, validation, and clinical application.

Ondansetron is used in clinical settings as an antiemetic drug. Although the animal studies showed its potential effectiveness also in treating neuropathic pain, the results from humans are inconclusive. The lack of efficacy of ondansetron in a subset of patients might be due to the overexpression of P-glycoprotein, which could result in low concentrations of ondansetron in the central nervous system (CNS). A surrogate of the CNS exposure might be drug concentration in the cerebrospinal fluid (CSF), especially in humans, as assessing the drug disposition directly in the patient's brain would be challenging. The study aimed to develop a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine concentrations of ondansetron in human K3EDTA plasma and CSF. Ondansetron was extracted from biological matrices by liquid-liquid extraction. The quantification was performed on a Sciex QTRAP 6500+ mass spectrometer with labeled ondansetron as an internal standard. The calibration range was 0.25-350 ng/mL in plasma and 0.025-100 ng/mL in CSF; for both matrices, 25 µL of samples was required for the assays. The method was validated according to the FDA and EMA guidelines and showed acceptable results. A pilot study confirmed its suitability for clinical samples: after 4-16 mg of intravenous ondansetron, the determined concentrations in plasma were 1.22-235.90 ng/mL, while in CSF - 0.018-11.93 ng/mL. In conclusion, the developed method fulfilled all validation requirements and can be applied to pharmacokinetic studies assessing the CNS ondansetron exposure in humans. The method's advantages, such as a low volume of matrix and a wide calibration range, support its use in a study in which rich sampling and various drug doses are expected.

Harnessing the conditioned pain modulation response in migraine diagnosis, outcome prediction, and treatment-A narrative review.

OBJECTIVE: To present the potential use and relevance of the conditioned pain modulation (CPM) response to migraine diagnosis, outcome prediction, and treatment. BACKGROUND: The CPM response is a widely used laboratory test to examine inhibitory pain modulation capabilities. METHODS: This narrative review summarizes and synthesizes the findings on the CPM response in patients with migraine. RESULTS: For diagnosis, we summarized the studies comparing CPM responses between patients with migraine and individuals without migraine or with other headache syndromes, as well as between patients with subtypes of migraine. For prediction, we summarized the studies utilizing the CPM response to predict migraine outcome, such as response to interventions. For treatment, we described a device that utilizes the CPM response for acute and preventative migraine treatment. In addition, we suggest the requirements needed for the CPM response to be used for migraine diagnosis, outcome prediction, and treatment. CONCLUSIONS: Although more research is needed, the CPM response could be a useful tool for improving migraine management.

Joint European Academy of Neurology-European Pain Federation-Neuropathic Pain Special Interest Group of the International Association for the Study of Pain guidelines on neuropathic pain assessment.

BACKGROUND AND PURPOSE: In these guidelines, we aimed to develop evidence-based recommendations for the use of screening questionnaires and diagnostic tests in patients with neuropathic pain (NeP). METHODS: We systematically reviewed studies providing information on the sensitivity and specificity of screening questionnaires, and quantitative sensory testing, neurophysiology, skin biopsy, and corneal confocal microscopy. We also analysed how functional neuroimaging, peripheral nerve blocks, and genetic testing might provide useful information in diagnosing NeP. RESULTS: Of the screening questionnaires, Douleur Neuropathique en 4 Questions (DN4), I-DN4 (self-administered DN4), and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) received a strong recommendation, and S-LANSS (self-administered LANSS) and PainDETECT weak recommendations for their use in the diagnostic pathway for patients with possible NeP. We devised a strong recommendation for the use of skin biopsy and a weak recommendation for quantitative sensory testing and nociceptive evoked potentials in the NeP diagnosis. Trigeminal reflex testing received a strong recommendation in diagnosing secondary trigeminal neuralgia. Although many studies support the usefulness of corneal confocal microscopy in diagnosing peripheral neuropathy, no study specifically investigated the diagnostic accuracy of this technique in patients with NeP. Functional neuroimaging and peripheral nerve blocks are helpful in disclosing pathophysiology and/or predicting outcomes, but current literature does not support their use for diagnosing NeP. Genetic testing may be considered at specialist centres, in selected cases. CONCLUSIONS: These recommendations provide evidence-based clinical practice guidelines for NeP diagnosis. Due to the poor-to-moderate quality of evidence identified by this review, future large-scale, well-designed, multicentre studies assessing the accuracy of diagnostic tests for NeP are needed.

An individualised tapering protocol reduces opioid use 1 year after spine surgery: A randomised controlled trial of patients with preoperative opioid use.

BACKGROUND: Persistent opioid use following surgery is common especially in patients with preoperative opioid use. This study aims to determine the long-term effect of an individualised opioid tapering plan versus standard of care in patients with a preoperative opioid use undergoing spine surgery at Aarhus University Hospital, Denmark. METHODS: This is the 1-year follow-up of a prospective, single-centre, randomised trial of 110 patients who underwent elective spine surgery for degenerative disease. The intervention was an individualised tapering plan at discharge and telephone counselling 1 week after discharge, compared to standard of care. Postoperative outcomes after 1 year include opioid use, reasons for opioid use and pain intensity. RESULTS: The overall response rate to the 1-year follow-up questionnaire was 94% (intervention group 52/55 patients and control group 51/55 patients). Forty-two patients (proportion = 0.81, 95% CI 0.67-0.89) in the intervention group compared to 31 (0.61, 95% CI 0.47-0.73; p = .026) patients in the control group succeeded in tapering to zero 1 year after discharge (p = .026). One patient (0.02, 95% CI 0.01-0.13) in the intervention group compared to seven patients (0.14, 95% CI 0.07-0.26) in the control group were unable to taper to their preoperative dose 1 year after discharge (p = .025). Back/neck and radicular pain intensity was similar between study groups. CONCLUSION: These results suggest that an individualised tapering plan at discharge combined with telephone counselling 1 week after discharge can reduce opioid use 1 year after spine surgery.

Establishing the Reliability, Validity, and Prognostic Utility of the Momentary Pain Catastrophizing Scale for Use in Ecological Momentary Assessment Research.

Despite the marked increase in ecological momentary assessment research, few reliable and valid measures of momentary experiences have been established. The goal of this preregistered study was to establish the reliability, validity, and prognostic utility of the momentary Pain Catastrophizing Scale (mPCS), a 3-item measure developed to assess situational pain catastrophizing. Participants in 2 studies of postsurgical pain outcomes completed the mPCS 3 to 5 times per day prior to surgery (N = 494, T = 20,271 total assessments). The mPCS showed good psychometric properties, including multilevel reliability and factor invariance across time. Participant-level average mPCS was strongly positively correlated with dispositional pain catastrophizing as assessed by the Pain Catastrophizing Scale (r = .55 and .69 in study 1 and study 2, respectively). To establish prognostic utility, we then examined whether the mPCS improved prediction of postsurgical pain outcomes above and beyond one-time assessment of dispositional pain catastrophizing. Indeed, greater variability in momentary pain catastrophizing prior to surgery was uniquely associated with increased pain immediately after surgery (b = .58, P = .005), after controlling for preoperative pain levels and dispositional pain catastrophizing. Greater average mPCS score prior to surgery was also uniquely associated with lesser day-to-day improvement in postsurgical pain (b = .01, P = .003), whereas dispositional pain catastrophizing was not (b = -.007, P = .099). These results show that the mPCS is a reliable and valid tool for ecological momentary assessment research and highlight its potential utility over and above retrospective measures of pain catastrophizing. PERSPECTIVE: This article presents the psychometric properties and prognostic utility of a new measure to assess momentary pain catastrophizing. This brief, 3-item measure will allow researchers and clinicians to assess fluctuations in pain catastrophizing during individuals' daily lives, as well as dynamic relationships between catastrophizing, pain, and related factors.

Advances in diagnosis and management of distal sensory polyneuropathies.

Distal sensory polyneuropathy (DSP) is characterised by length-dependent, sensory-predominant symptoms and signs, including potentially disabling symmetric chronic pain, tingling and poor balance. Some patients also have or develop dysautonomia or motor involvement depending on whether large myelinated or small fibres are predominantly affected. Although highly prevalent, diagnosis and management can be challenging. While classic diabetes and toxic causes are well-recognised, there are increasingly diverse associations, including with dysimmune, rheumatological and neurodegenerative conditions. Approximately half of cases are initially considered idiopathic despite thorough evaluation, but often, the causes emerge later as new symptoms develop or testing advances, for instance with genetic approaches. Improving and standardising DSP metrics, as already accomplished for motor neuropathies, would permit in-clinic longitudinal tracking of natural history and treatment responses. Standardising phenotyping could advance research and facilitate trials of potential therapies, which lag so far. This review updates on recent advances and summarises current evidence for specific treatments.

Factors associated with persistent postsurgical pain after total knee or hip joint replacement: a systematic review and meta-analysis.

Studies have identified demographic, clinical, psychosocial, and perioperative variables associated with persistent pain after a variety of surgeries. This study aimed to perform a systematic review and meta-analysis of factors associated with persistent pain after total knee replacement (TKR) and total hip replacement (THR) surgeries. To meet the inclusion criteria, studies were required to assess variables before or at the time of surgery, include a persistent postsurgical pain (PPSP) outcome measure at least 2 months after a TKR or THR surgery, and include a statistical analysis of the effect of the risk factor(s) on the outcome measure. Outcomes from studies implementing univariate and multivariable statistical models were analyzed separately. Where possible, data from univariate analyses on the same factors were combined in a meta-analysis. Eighty-one studies involving 171,354 patients were included in the review. Because of the heterogeneity of assessment methods, only 44% of the studies allowed meaningful meta-analysis. In meta-analyses, state anxiety (but not trait anxiety) scores and higher depression scores on the Beck Depression Inventory were associated with an increased risk of PPSP after TKR. In the qualitative summary of multivariable analyses, higher preoperative pain scores were associated with PPSP after TKR or THR. This review systematically assessed factors associated with an increased risk of PPSP after TKR and THR and highlights current knowledge gaps that can be addressed by future research.

Perspectives on Participation in Clinical Trials Among Individuals With Pain, Depression, and/or Anxiety: An ACTTION Scoping Review.

For individuals experiencing pain, the decision to engage in clinical trials may be influenced by a number of factors including current and past care, illness severity, physical functioning, financial stress, and caregiver support. Co-occurring depression and anxiety may add to these challenges. The aim of this scoping review was to describe perspectives about clinical trial participation, including recruitment and retention among individuals with pain and pain comorbidities, including depression and/or anxiety. We searched PubMed, CINAHL, PsycINFO, and Cochrane CENTRAL databases. Study features, sample demographics, perspectives, barriers and/or motivations were collected and described. A total of 35 assessments were included in this scoping review with 24 focused on individuals with pain (24/35, 68.6%), 9 on individuals with depression and/or anxiety (9/35, 25.7%), and 2 on individuals with pain and co-occurring depression/anxiety (2/35, 5.7%). Barriers among participants with pain and those with depression included: research team's communication of information, fear of interventional risks, distrust (only among respondents with pain), too many procedures, fear of inadequate treatment, disease-life stressors, and embarrassment with study procedures (more commonly reported in participants with depression). Facilitators in both groups included: altruism and supportive staff, better access to care, and the ability to have outcome feedback (more commonly among individuals with depression). Individuals with pain and depression experience challenges that affect trial recruitment and retention. Engaging individuals with pain within research planning may assist in addressing these barriers and the needs of individuals affected by pain and/or depression. PERSPECTIVE: This review highlights the need to address barriers and facilitators to participation in clinical trials, including the need for an assessment of perspectives from underserved or marginalized populations.

Relief of chronic pain associated with increase in midline frontal theta power.

Introduction: There is a need to identify objective cortical electrophysiological correlates for pain relief that could potentially contribute to a better pain management. However, the field of developing brain biomarkers for pain relief is still largely underexplored. Objectives: The objective of this study was to investigate cortical electrophysiological correlates associated with relief from chronic pain. Those features of pain relief could serve as potential targets for novel therapeutic interventions to treat pain. Methods: In 12 patients with chronic pain in the upper or lower extremity undergoing a clinically indicated nerve block procedure, brain activity was recorded by means of electroencephalogram before and 30 minutes after the nerve block procedure. To determine the specific cortical electrophysiological correlates of relief from chronic pain, 12 healthy participants undergoing cold-pressor test to induce experimental acute pain were used as a control group. The data were analyzed to characterize power spectral density patterns of pain relief and identify their source generators at cortical level. Results: Chronic pain relief was associated with significant delta, theta, and alpha power increase at the frontal area. However, only midfrontal theta power increase showed significant positive correlation with magnitude of reduction in pain intensity. The sources of theta power rebound were located in the left dorsolateral prefrontal cortex (DLPFC) and midline frontal cortex. Furthermore, theta power increase in the midline frontal cortex was significantly higher with chronic vs acute pain relief. Conclusion: These findings may provide basis for targeting chronic pain relief via modulation of the midline frontal theta oscillations.