Unpredictable Pain Research Articles

Biobehavior Life Regulation (BLR) scale for living well in chronic pain: Preliminary scale development and validation.

Currently available pain assessment scales focus on pain-related symptoms and limitations imposed by pain. Validated assessment tools that measure how pain is regulated by those who live well with pain are missing. This study seeks to fill this gap by describing the development and preliminary validation of the Biobehavior Life Regulation (BLR) scale. The BLR scale assesses engagement, social relatedness, and self-growth in the presence of chronic pain and the unpredictability of chronic pain. Sources for items included survivor strategies, patient experiences, existing scales, and unpredictable pain research. Review for suitability yielded 52 items. Validation measures were identified for engagement, social relatedness, self-growth, and unpredictability of pain. The study sample (n = 202) represented patients treated in the Phoenix VA Health Care System (n = 112) and two community clinics (n = 90). Demographic characteristics included average age of 52.5, heterogeneous in ethnicity and race at the VA, mainly Non-Hispanic White at the community clinics, 14 years of education, and pain duration of 18 years for the VA and 15.4 years for community clinics. Exploratory factor analysis using Oblimin rotation in the VA sample (n = 112) yielded a two-factor solution that accounted for 48.23% of the total variance. Confirmatory factor analysis (CFA) in the same sample showed high correlations among items in Factor 1, indicating redundancy and the need to further reduce items. The final CFA indicated a 2-factor solution with adequate fit to the data. The 2-factor CFA was replicated in Sample 2 from the community clinics (n = 90) with similarly adequate fit to the data. Factor 1, Pain Regulation, covered 8 items of engagement, social relatedness, and self-growth while Factor 2, Pain Unpredictability, covered 6 items related to the experience of unpredictable pain. Construct validity showed moderate to higher Pearson correlations between BLR subscales and relevant well-established constructs that were consistent across VA and community samples. The BLR scale assesses adaptive regulation strategies in unpredictable pain as a potential tool for evaluating regulation resources and pain unpredictability.

The effect of unpredictability on the perception of pain: a systematic review and meta-analysis.

Despite being widely assumed, the worsening impact of unpredictability on pain perception remains unclear because of conflicting empirical evidence, and a lack of systematic integration of past research findings. To fill this gap, we conducted a systematic review and meta-analysis focusing on the effect of unpredictability on pain perception. We also conducted meta-regression analyses to examine the moderating effect of several moderators associated with pain and unpredictability: stimulus duration, calibrated stimulus pain intensity, pain intensity expectation, controllability, anticipation delay, state and trait negative affectivity, sex/gender and age of the participants, type of unpredictability (intensity, onset, duration, location), and method of pain induction (thermal, electrical, mechanical pressure, mechanical distention). We included 73 experimental studies with adult volunteers manipulating the (un)predictability of painful stimuli and measuring perceived pain intensity and pain unpleasantness in predictable and unpredictable contexts. Because there are insufficient studies with patients, we focused on healthy volunteers. Our results did not reveal any effect of unpredictability on pain perception. However, several significant moderators were found, ie, targeted stimulus pain intensity, expected pain intensity, and state negative affectivity. Trait negative affectivity and uncontrollability showed no significant effect, presumably because of the low number of included studies. Thus, further investigation is necessary to clearly determine their role in unpredictable pain perception.

Assessing coagulopathy and endothelial dysfunction in pediatric venous malformation: A thromboelastometry and syndecan-1 study.

The occurrence of unpredictable pain crises are the principal determinant of the quality of life for patients with venous malformations (VM). A definite coagulation phenomenon, characterized by an increase in D-dimer levels and the presence of phleboliths within the malformation, has been previously reported. By applying Virchow's triad and evaluating intralesional samples, our objective is to delineate the coagulation profile and the extent of endothelial dysfunction within the malformation. With the authorization of the Ethics Committee, a research project was undertaken on intralesional and extralesional blood samples from 30 pediatric patients afflicted with spongiform VM. Thromboelastometry analyses were performed using ROTEM Sigma, and the concentration of syndecan-1 was determined by ELISA. In the ROTEM analyses, the A5, A10, and maximum clot firmness (MCF) values were below the established reference ranges in the intralesional samples in both the EXTEM and INTEM assays, indicating that intralesional clots had significant instability. Furthermore, during the investigation of the delayed fibrinolysis phase using recombinant tissue plasminogen activator (rtPA) in EXTEM analysis, widespread hyperfibrinolysis was observed intralesional. Additionally, analysis of syndecan-1 showed significant differences between extralesional and intralesional levels (p<.026) and controls (p<.03), suggesting differences in the state of endothelium. For the first time, we developed a comprehensive understanding of the coagulopathic profile of VM and the role of endothelial dysfunction in its pathogenesis. These findings will enable the implementation of targeted therapies based on the individual coagulation profiles.

Roles of Pharmacists in the Management of Sickle Cell Disease in Adults: A Narrative Review.

Background: Sickle cell disease (SCD) is an autosomal, recessive, genetic condition of the sickle cell genes. It affects about 100 000 people in the United States where an estimated 1 out of every 365 black children and 1 out of every 13 black children will be born with SCD and sickle cell trait, respectively. Severe and unpredictable pain crisis are the leading cause of emergency department visit for adult patients with SCD and account for 90% of inpatient hospitalizations and 85% of all acute medical care, as well as high usage of medical resources. The care of patients with SCD is complex and requires a multidisciplinary approach. With a few pharmacotherapeutic options to reduce SCD complications and pain episodes, the role of pharmacists in the medication management is unclear. This article aims to outline the potential role of pharmacists in SCD management. Data sources: The authors searched Medline, PubMed, EMBASE, and Scopus from January 1, 1990 to August 31, 2022, for primary literature that assessed the role of pharmacists in managing patients with SCD. Results: The authors identified relevant studies and summarized the role of pharmacists in SCD management. Conclusions: Access to comprehensive health care is essential to ensure that patients with SCD have decreased hospitalizations and good health-related quality of life. Pharmacists are an integral part of the multidisciplinary health-care team and can help patients with SCD navigate the complexities of health care. Pharmacists are medication experts who are positioned to ensure comprehensive care in the acute and chronic SCD management.

Real-World Experience of Individuals with Sickle Cell Disease Treated with Voxelotor: Initial Report from the Multicenter, Prospective Prospect Study

Introduction: Sickle cell disease (SCD) is an inherited blood disorder in which sickle hemoglobin (HbS) polymerization results in red blood cell sickling, which in turn leads to chronic hemolytic anemia, unpredictable pain episodes, and recurrent vaso-occlusive crises (VOCs). Hemolysis and low hemoglobin (Hb) are associated with organ damage, increased morbidity, and early mortality. Voxelotor, a first-in-class HbS polymerization inhibitor, is approved in the US for the treatment of patients with SCD aged ≥4 years and in Europe for the treatment of hemolytic anemia due to SCD in patients aged ≥12 years. In the phase 3, randomized, controlled HOPE (NCT03036813) and the phase 2, open-label HOPE-KIDS 1 (NCT02850406) trials, patients treated with once daily oral voxelotor experienced increased Hb levels and reductions in markers of hemolysis at Week 24 compared with baseline. Here we report the first efficacy and safety data from patients with SCD enrolled in the prospective PROSPECT registry who received voxelotor in a real-world setting. Methods: PROSPECT (NCT04930445) is a post-marketing, open-label, observational, prospective patient registry of patients with SCD (aged ≥4 years) in the US. Eligible participants are being treated with voxelotor as prescribed by their physician as part of their usual care. Participants are treated and evaluated per standard of care and at the physician's discretion. Treatment, including interruptions and restarting treatment, continue at the discretion of the treating physician. Patients receive any additional medications or transfusions as determined and prescribed by their physician. Follow-up duration is 5 years after the first dose of voxelotor therapy. Study data are collected from patient medical records and secondary data sources and entered in case report forms via an electronic data capture system. Results: At data cutoff (May 30, 2023), 85 patients were enrolled at 5 sites. The mean (SD) age was 33.2 (15.3) years, 51.8% of patients were female, and most (92.9%) were Black or African American. Overall, 72.9% of patients were genotype HbSS, 62.4% were taking concurrent hydroxyurea, and mean (SD) Hb at baseline was 7.7 (1.53) g/dL. The mean (SD) duration of treatment, excluding gaps, was 47.0 (12.35) weeks. At the data cutoff, 76 patients (89.4%) continued voxelotor treatment; 7 patients (8.2%) never started voxelotor, and 2 patients (2.4%) discontinued treatment because of adverse events (AEs).The initial prescribed daily doses of voxelotor were 1500 mg (84.7%), 1000 mg (8.2%), 900 mg (4.7%), or 500 mg (2.4%). The most common reasons for prescribing voxelotor were to reduce either anemia (74.1%), frequency of VOCs (15.3%), pain (14.1%), or the frequency of blood transfusion (9.4%); multiple reasons could be selected. In 66 patients with recorded baseline and posttreatment Hb values, the observed mean (SD) peak posttreatment Hb value was 9.0 (1.75) g/dL, representing a mean (SD) increase from baseline of 1.3 (1.25) g/dL. The range of peak Hb change from baseline was −1.4 to 4.6 g/dL and 52/66 patients (78.8%) had a positive Hb response (Figure). Reductions in markers of hemolysis were also observed following voxelotor treatment, with nadir mean (SD) decreases from baseline of −23.9% (55.92%) in reticulocyte percentage (n=54), −1.8 (2.36) mg/dL in total bilirubin (n=61), and −1.6 (1.95) mg/dL in indirect bilirubin (n=38). AEs of special interest reported in &amp;gt;3% of patients included diarrhea, headache, nausea, abdominal pain, and rash (Table); most of these AEs were mild or moderate in severity. Conclusions: PROSPECT is the first prospective patient registry of voxelotor, with the potential to follow up to 1000 participants for up to 5 years and enable long-term, robust data collection of real-world care patterns that could inform how best to incorporate voxelotor into the treatment paradigm of patients with SCD. In this initial cohort of participants enrolled to date, following voxelotor treatment for a mean duration of 47.0 weeks, the mean peak increase from baseline in Hb was 1.3 g/dL, and associated reductions in markers of hemolysis were observed. Safety data were consistent with the phase 3 HOPE and HOPE-KIDS 1 trials. Overall, these initial findings provide support for the real-world safety, tolerability, and effectiveness of voxelotor treatment in individuals with SCD. While enrollment is ongoing, updated data will be regularly reported.

Expectations underlie the effects of unpredictable pain: a behavioral and electroencephalogram study.

Previous studies on the potential effects of unpredictability on pain perception and its neural correlates yielded divergent results. This study examined whether this may be explained by differences in acquired expectations. We presented 41 healthy volunteers with laser heat stimuli of different intensities. The stimuli were preceded either by predictable low, medium, or high cues or by unpredictable low-medium, medium-high, or low-high cues. We recorded self-reports of pain intensity and unpleasantness and laser-evoked potentials (LEPs). Furthermore, we investigated whether dynamic expectations that evolved throughout the experiment based on past trials were better predictors of pain ratings than fixed (nonevolving) expectations. Our results replicate previous findings that unpredictable pain is higher than predictable pain for low-intensity stimuli but lower for high-intensity stimuli. Moreover, we observed higher ratings for the medium-high unpredictable condition than the medium-low unpredictable condition, in line with an effect of expectation. We found significant interactions (N1, N2) for the LEP components between intensity and unpredictability. However, the few significant differences in LEP peak amplitudes between cue conditions did not survive correction for multiple testing. In line with predictive coding perspectives, pain ratings were best predicted by dynamic expectations. Surprisingly, expectations of reduced precision (increased variance) were associated with lower pain ratings. Our findings provide strong evidence that (dynamic) expectations contribute to the opposing effects of unpredictability on pain perception; therefore, we highlight the importance of controlling for them in pain unpredictability manipulations. We also suggest to conceptualize pain expectations more often as dynamic constructs incorporating previous experiences.

Effectiveness of cartoon video as a distraction strategy on pain perception during venepuncture among children

Pain is often a subjective sensation having physiological, psychological and emotional implications for an individual. In a hospital setting, children usually perceive unpredictable pain which is often procedure related that can impact both emotionally and psychologically. Perception of pain varies with multiple factors such as age, gender, intellectual level, personality, parental care and previous experience of painful procedure/ suppression of pain using pharmacologic and non-pharmacologic measures. Our study aimed to assess the effectiveness of animated cartoons as a distraction strategy to reduce behavioral response to pain perception among children undergoing venepuncture and to assess and compare pain perception in children with and without cartoon distraction. We had total of 60 children participated in the study group, we found that children who were distracted perceived less pain (p &lt; 0.001), also the number of attempts required to do venepuncture also reduced significantly (p &lt; 0.001). We concluded that, distraction technique is a simple yet effective tool in alleviating pain during venepuncture in preschool children. This technique can help in reduction of anxiety among children.

Association of Pain Sensitization and Conditioned Pain Modulation to Pain Patterns in Knee Osteoarthritis.

To examine the cross-sectional association of ascending pain mechanisms, implicated in pain sensitization, and descending pain modulation with pain patterns and unpredictability of pain. The Multicenter Osteoarthritis Study is a longitudinal cohort of older adults with or at risk of knee osteoarthritis. Peripheral and central ascending pain mechanisms were assessed using quantitative sensory tests, pressure pain thresholds using a handheld pressure algometer (knee/peripheral and wrist/central), and temporal summation using weighted probes (wrist/central). Descending modulation was assessed by conditioned pain modulation using pressure pain thresholds and a forearm ischemia test. Pain patterns were characterized based on responses to the Intermittent and Constant Osteoarthritis Pain questionnaire: 1) no intermittent or constant pain, 2) intermittent pain only, 3) constant pain only, and 4) combined constant and intermittent pain. A question regarding frequency assessed unpredictable pain. We assessed the association of quantitative sensory test measures to pain patterns using regression models with generalized estimating equations. There were 2,794 participants (mean age 63.9 years, body mass index 29.5 kg/m2 , and 57% female). Lower pain sensitization by wrist pressure pain threshold (odds ratio [OR] 0.80 [95% confidence interval (95% CI) 0.68, 0.93]) and adequate conditioned pain modulation (OR 1.45 [95% CI 1.10, 1.92]) were associated with having constant ± intermittent pain compared with intermittent pain only. Higher pain sensitization (by pressure pain thresholds and temporal summation) was associated with a higher likelihood of unpredictable pain. Knee pain patterns appear to be related to peripheral ± central facilitated ascending pain mechanisms and descending modulatory mechanisms. These findings highlight the need for a broader approach to understanding pain mechanisms by symptomatic disease progression.

Classification of Pain Dynamics in Sickle Cell Disease from Mobile App Reporting

Background: Sickle Cell Disease (SCD) is a chronic blood disorder in which complications result from vaso-occlusion. Pain is the most common symptom reported in patients with SCD and includes both acute unpredictable pain as well as chronic pain. Chronic pain is clinically defined as having more days with pain than without pain over a period of 6 months. Various classifications systems have been developed to better understand pain phenotypes, however, there is variability in data and groupings of patients. Recent work based on patient-reported outcome data has shown that patients may be classified into three subgroups: infrequent acute pain, limited recent pain with moderate long-term pain, and persistent severe pain.An improved understanding of the ways in which pain dynamics manifest over time will allow patients and medical providers to better manage pain. Using previously-published data which collected self-reported data through a mobile app over 6 months (Clifton et al., 2017, J. Comput. Biol.), we aimed to characterize the different ways in which patients experienced pain over time. In this work, we sought to identify classes of patients based only on their self reported pain levels.Methods: Patients within the previously-published study were asked to self-report their pain levels from 0-10 on a daily basis through a mobile app. The study included 39 patients (16 male, 23 female), with a mean age of 33.4. Patients reported their pain an average of 0.4 times per day over an average of 164.6 days.To allow for the possibility that patients' experiences change over time, we windowed the time series of pain dynamics into non-overlapping two-week windows. Within each window, the data were linearly interpolated to regularly-spaced samples. Then, we applied spectral clustering to identify classes of similar pain trajectories within the windowed data.Within the data, we also identified patients with and without chronic pain within the sample based on whether or not they have taken long-acting opioid medications, which are commonly prescribed for those with a diagnosis of chronic pain. With this identification, we compared patients within the identified classes with patients diagnosed with chronic pain.Results: We found that three classes of pain dynamics may be identified from the data considered: class I, class II, and class III (Figure). Class I pain trajectories have mild baseline pain, typically 0, with acute exacerbations of low to medium pain levels. Class II trajectories show moderate mean pain values, and show large variation within each trajectory. Class III trajectories show consistently high pain levels, rarely dropping below 7.All three classes include patients who have been diagnosed with chronic pain, but the proportion of patients with chronic pain differs. Patients with chronic pain represented 32% of samples in class I, 83% of samples in class II, and 86% of samples in class III.Conclusions: Based only on self-reported pain over time, clustering pain experiences into classes yields three distinct classes. These classes do not perfectly align with chronic pain diagnoses, but classes II and III both contain mostly chronic pain patients. Based on this and the unique behaviors of those classes, it may be useful to differentiate chronic pain into persistent chronic pain and intermittent chronic pain. Moreover, the findings of these classes are similar to results found from analyzing patient reported outcomes and show promise for the continued use of mHealth apps to acquire patient reported symptoms. [Display omitted] DisclosuresShah: CSL Behring: Consultancy; Emmaus: Consultancy; Novartis: Research Funding, Speakers Bureau; Bluebird Bio: Consultancy; Guidepoint Global: Consultancy; GLG: Consultancy; Alexion: Speakers Bureau; GBT: Consultancy, Research Funding, Speakers Bureau.

A systematic literature review of frequency of vaso-occlusive crises in sickle cell disease

Background and purposeSickle cell disease (SCD) is a collection of rare inherited blood disorders affecting approximately 100,000 people in the U.S. and 20–25 million people globally. Individuals with SCD experience recurrent episodes of severe and unpredictable pain that are caused by vaso-occlusive crises (VOCs), a hallmark of the disease. VOCs are the primary cause of hospitalization in SCD, result in missed workdays and school days, and decrease quality of life (QoL). Although VOCs cause significant burden in the lives of individuals with SCD, there is no synthesis on the frequency of VOCs in the real world. This systematic literature review sought to identify literature describing the frequency of VOCs experienced by individuals with SCD in real-world settings.MethodsMEDLINE and 6 congresses were searched (date range: January 1, 2000 to June 30, 2020). Studies were reviewed independently by two researchers. Studies assessing frequency or prevalence of VOCs or VOC-related outcomes were included.ResultsOf 1438 studies identified in the search, 52 met pre-specified inclusion and exclusion criteria. Reported frequency of VOCs varied widely ranging from a mean or median of 0 VOCs/year to 18.2 VOCs/year. The proportion of patients experiencing ≥ 3 VOCs/year ranged from 4 to 67% and the proportion of patients experiencing ≥ 5 VOCs/year ranged from 18 to 59%. Measures of VOC severity were limited, with 13 studies considering frequency of complicated VOCs and only 1 study reporting duration of VOC episodes.ConclusionsThis is the first study to systematically assess published evidence pertaining to VOCs in real-world settings. Reported VOC frequency in real-world settings varied widely, with a majority of studies only considering VOCs managed in an inpatient or outpatient setting. Studies that considered VOCs managed at home reported a higher frequency of VOCs, suggesting that many studies may underestimate the frequency of VOCs. This systematic literature review (SLR) highlights the need for consistent reporting of (1) self-reported VOCs, including those managed at home, (2) definitions of VOCs, (3) complicated VOCs, and (4) duration of VOC episodes in literature.

Global geographic differences in healthcare utilization for sickle cell disease pain crises in the CASiRe cohort

BackgroundSickle cell disease (SCD) is characterized by frequent, unpredictable pain episodes and other vaso-occlusive crises (VOCs) leading to significant healthcare utilization. VOC frequency is often an endpoint in clinical trials investigating novel therapies for this devastating disease. ProcedureThe Consortium for the Advancement of Sickle Cell Research (CASiRe) is an international collaboration investigating clinical severity in SCD using a validated questionnaire and medical chart review standardized across four countries (United States, United Kingdom, Italy and Ghana). ResultsThis study, focused on pain crisis incidence and healthcare utilization, included 868 patients, equally represented according to age and gender. HgbSS was the most common genotype. Patients from Ghana used the Emergency Room/Day Hospital for pain more frequently (annualized mean 2.01) than patients from other regions (annualized mean 1.56 U.S.; 1.09 U.K.; 0.02 Italy), while U.K. patients were hospitalized for pain more often (annualized mean: U.K. 2.98) than patients in other regions (annualized mean 1.98 U.S.; 1.18 Ghana; Italy 0.54). Italy's hospitalization rate for pain (annualized mean: 0.57) was nearly 20 times greater than its emergency room/day hospital only visits for pain (annualized mean: 0.03). When categorized by genotype and age, similar results were seen. ConclusionsGeographic differences in pain crisis frequency and healthcare utilization may correlate with variable organization of healthcare systems among countries and should be considered regarding trial design, endpoints, and analysis of results when investigating novel agents for clinical benefit.

Beyond Average: Providers' Assessments of Indices for Measuring Pain Intensity in Patients With Chronic Pain.

Introduction: Effective clinical care for chronic pain requires accurate, comprehensive, meaningful pain assessment. This study investigated healthcare providers' perspectives on seven pain measurement indices for capturing pain intensity.Methods: Semi-structured telephone interviews were conducted with a purposeful sample from four US regions of 20 healthcare providers who treat patients with chronic pain. The qualitative interview guide included open-ended questions to address perspectives on pain measurement, and included quantitative ratings of the importance of seven indices [average pain, worst pain, least pain, time in no/low pain, time in high pain, fluctuating pain, unpredictable pain]. Qualitative interview data were read, coded and analyzed for themes and final interpretation. Standard quantitative methods were used to analyze index importance ratings.Results: Despite concerns regarding 10-point visual analog and numeric rating scales, almost all providers used them. Providers most commonly asked about average pain, although they expressed misgivings about patient reporting and the index's informational value. Some supplemented average with worst and least pain, and most believed pain intensity is best understood within the context of patient functioning. Worst pain received the highest mean importance rating (7.60), average pain the second lowest rating (5.65), and unpredictable pain the lowest rating (5.20).Discussion: Assessing average pain intensity obviates obtaining clinical insight into daily contextual factors relating to pain and functioning. Pain index use, together with timing, functionality and disability, may be most effective for understanding the meaning to patients of high pain, how pain affects their life, how life affects their pain, and how pain changes and responds to treatment.

Global Geographic Differences in Healthcare Utilization for Sickle Cell Disease Pain Crises in the CASiRe Cohort

Background: Sickle cell disease (SCD) is characterized by frequent, unpredictable pain episodes and other vaso-occlusive crises (VOCs) leading to significant healthcare utilization. VOC frequency is often an endpoint in clinical trials investigating novel therapies for this devastating disease. Procedure: The Consortium for the Advancement of Sickle Cell Research (CASiRe) is an international collaboration investigating clinical severity in SCD using a validated questionnaire and medical chart review standardized across four countries (United States, United Kingdom, Italy and Ghana). Results: This study, focused on pain crisis incidence and healthcare utilization, included 868 patients, equally represented according to age and gender. HgbSS was the most common genotype. Patients from Ghana used the Emergency Room/Day Hospital for pain more frequently (annualized mean 2.01) than patients from other regions (annualized mean 1.56 U.S.;1.09 U.K.; 0.02 Italy), while U.K. patients were hospitalized for pain more often (annualized mean: U.K. 2.98) than patients in other regions (annualized mean 1.98 U.S.; 1.18 Ghana; Italy 0.54). Italy’s hospitalization rate for pain (annualized mean: 0.57) was nearly 20 times greater than its emergency room/day hospital only visits for pain (annualized mean: 0.03). When categorized by genotype and age, similar results were seen. Conclusions: Geographic differences in pain crisis frequency and healthcare utilization may correlate with variable organization of healthcare systems among countries and should be considered regarding trial design, endpoints, and analysis of results when investigating novel agents for clinical benefit. Funding: This study was supported in part by research funding from Grant # NIMHD T37MD001425 to AC. Declaration of Interest: A Campbell: research funding and consultancy from Global Blood Therapeutics (GBT), Novartis; and consultancy for bluebird bio; D Manwani: research funding from Grifols; consultancy for Novartis, Pfizer, Global Blood Therapeutics; B Andemariam: consultancy for Bluebird bio, CRISPR/Vertex, Forma Therapeutics, Global Blood Therapeutics, Hemanext, Novartis, NovoNordisk, Cyclerion, Terumo, Roche, Sanofi-Genzyme; research funding from Global Blood Therapeutics, Imara, Novartis; B Inusa: education funding from Novartis AstraZeneca, Global Blood Therapeutics, Celgene, Vertex; C Strunk: consultancy for Global Blood Therapeutics, Forma Therapeutics, Novartis and Medunik USA; R Colombatti: research funding from Global Blood Therapeutics, BlueBird Bio; consultancy for Novartis, Addmedica, NovoNordisk; C Piccone: consultancy for Global Blood Therapeutics and Novartis; W Zempsky: consultancy for Glycomimetics and GlaxoSmithKleine. No disclosures to declare from the other co-authors. Ethical Approval: This study received IRB approval at each institution.

Awake Endospine Disektomi pada Pasien Lumbar Spinal Stenosis karena Hernia Nucleus Pulposus

Lumbar spinal stenosis (LSS) are symptoms from degradation canalis spinalis vertebrae’s size which pressured nerve inside it. Based on its cause, there are two types of LSS, congenital and degenerative. The patient can experience an unpredictable pain phase as well as a stable phase without pain. Bulging of intervertebralis disc or HNP is one of degenerative LSS. HNP disease is one of the causes of low back pain and is a major health problem. HNP prevalention is 1-2 % from population. One of therapy use to medicate LSS is endospine discectomy. This operation done with general anesthesia (GA) or neuroaxial anesthesia (spinal, epidural). GA preferably used because it caused less side effect like airway obstruction or neural injury. Dexmedetomidine has a sedative effect without the risk of respiratory depression and has an analgesic effect. It can be used to awake endospine methods in dissectomy. In this case report, the writer did awake endospine method to accommodate operator so they could know level of pain and motoric function of patient durante operation.

The influence of perceived racial bias and health-related stigma on quality of life among children with sickle cell disease

ABSTRACT Objectives: Individuals with sickle cell disease (SCD) experience significant health problems that may result in unpredictable pain episodes and frequent healthcare utilization. Disparities in clinical care may contribute to health-related stigma and racial bias for this majority African-American/Black population. There is less known about the influence of health-related stigma and racial bias on the health-related quality of life (HRQOL) of children with SCD. In the present study, we assessed these relationships and identified differences across demographic factors (i.e. age, gender). Design: Data was collected from African American children with SCD aged 8–16 years (57% male, 63% HbSS). Children completed the Childhood Stigma Scale (adapted for SCD), the Child Perceptions of Racism in Children and Youth scale, and the Pediatric Quality of Life Inventory Sickle Cell Disease Module. Caregivers provided demographic information. Results: In the first regression model, health-related stigma (p = .007) predicted HRQOL, but neither age nor gender were significant predictors. In the second regression model, age (p = .03) predicted HRQOL, but neither gender nor racial bias were significant predictors. Of interest, there was a significant interaction between age, gender, and racial bias (p = .02). Specifically, older girls who reported high levels of perceived racial bias had poorer HRQOL. Conclusions: Our study highlights the need for increased awareness about the effects of health-related stigma and racial bias on HRQOL for children with SCD, particularly for older girls who endorse racial bias. Our findings will guide future stigma and bias reduction interventions that may meet the needs of older girls with SCD.

Racism and Health-Related Quality of Life in Pediatric Sickle Cell Disease: Roles of Depression and Support.

Sickle cell disease (SCD) is the most commonly inherited blood disorder in the United States, and it predominately affects the Black community. SCD is characterized by a number of symptoms, including unpredictable pain, which can lead to hospitalizations. Data indicate that people with SCD experience racism and ample data indicate that racism predicts depressive symptoms and impaired health-related quality of life (HRQOL). In contrast, research suggests that social support might buffer the impact of racism on depression. The aim of this study was to explore associations among perceived racism, depressive symptoms, and HRQOL in adolescents with SCD. Consistent with the literature, it was predicted that perceived racism would predict HRQOL through depression, and social support would moderate the negative impact of racism on depression. In a cross-sectional design, 75 inpatient adolescents with SCD completed measures of perceived racism, depressive symptoms, HRQOL, and social support. This results indicated a moderated mediation model with greater perceived racism predicting more depressive symptoms, which in turn related to poorer HRQOL; greater access to social support from individuals with SCD strengthened the perceived racism-depressive symptom association. Findings suggest a model for how racism, depressive symptoms, HRQOL, and social support might interact in hospitalized adolescents with SCD. Longitudinal or experimental designs are needed to substantiate directionality among these variables. Results highlight several areas for future research and clinical avenues to improve the welfare of youth with SCD.

Recovery despite everyday pain: Women's experiences of living with whiplash-associated disorder.

Living with whiplash-associated disorders (WAD) means living every day under the influence of pain and limitations. As the incidence of WAD and the related intensity of pain are somewhat higher among women than men, the aim of the present study was to describe women's experiences of living with WAD. A purposive sample of seven women participated in individual in-depth qualitative interviews, the transcripts of which were subjected to qualitative content analysis. The results of the analysis suggested six themes of women's experiences with WAD: living with unpredictable pain; trying to manage the pain; living with limitations; being unable to work as before; needing support and understanding; and learning to live with limitations. The findings showed that unpredictable pain limited women's strength to engage in activities of daily life and be as active as before. Support and understanding were important for their ability to manage changes in their daily lives. Pain considerably affects the daily lives of women with WAD, particularly by limiting their ability to perform activities and to enjoy their professional and social lives. As women with WAD need support with managing their daily lives, nurses and other healthcare personnel should adopt a person-centred approach, in order to support such women according to their individual needs and circumstances.

Imaging Brain Mechanisms of Functional Somatic Syndromes: Potential as a Biomarker?

When patients present with persistent bodily complaints that cannot be explained by a symptom-linked organic pathology (medically unexplained symptoms), they are diagnosed with 'functional' somatic syndromes (FSS). Despite their prevalence, the management of FSS is notoriously challenging in clinical practice. This may be because FSS are heterogeneous disorders in terms of etiopathogenesis. They include patients with primarily peripheral dysfunction, primarily centrally driven somatic symptoms, and a mix of both. Brain-imaging studies, particularly data-driven pattern recognition methods using machine learning algorithms, could provide brain-based biomarkers for these clinical conditions. In this review, we provide an overview of our brain imaging data on brain-body interactions in one of the most well-known FSS, irritable bowel syndrome (IBS), and discuss the possible development of a brain-based biomarker for FSS. Anticipation of unpredictable pain, which commonly elicits fear in FSS patients, induced increased activity in brain areas associated with hypervigilance during rectal distention and non-distention conditions in IBS. This was coupled with dysfunctional inhibitory influence of the medial prefrontal cortex (mPFC) and pregenual anterior cingulate cortex (pACC) on stress regulation systems, resulting in the activated autonomic nervous system (ANS) and neuroendocrine system stimulated by corticotropin-releasing hormone (CRH). IBS subjects with higher alexithymia, a risk factor for FSS, showed stronger activity in the insula during rectal distention but reduced subjective sensitivity. Reduced top-down regulation of the ANS and CRH system by mPFC and pACC, discordance between the insula response to stimulation and subjective sensation of pain, and stronger threat responses in hypervigilance-related areas may be a candidate brain-based biomarker.

P08 Beliefs about pain in juvenile idiopathic arthritis are significantly associated with higher reported pain and more negative affect in children and young people

Abstract Background Persistent, unpredictable pain is one of the most burdensome features of juvenile idiopathic arthritis (JIA) which is a relapsing-remitting inflammatory musculoskeletal condition presenting in children and young people under 16 years. Recent research into perceptions of illness in young people has found that conceptualisations of long-term disease are mainly about the most salient features and symptoms, not of the illness as a whole. Particularly in young people with JIA, perceptions of pain are central to the individuals’ beliefs about the chronic condition. In paediatric pain research in general, the study of pain beliefs has mainly focused on pain catastrophising. Associations between other potentially important pain beliefs and pain outcomes (e.g. reporting pain or well-being) have not been explored to date. The aim of this study was to explore a wide range of pain perceptions in young people with JIA and to investigate whether these pain beliefs were associated with pain severity or well-being. Methods Cross-sectional data from the largest UK cohort study of children with JIA were analysed (the Childhood Arthritis Prospective Study- CAPS). Participants aged over 11 years completed ‘The Pain Perceptions Questionnaire for Young People (PPQ–YP)’ which assesses pain beliefs corresponding to the Common Sense-Self Regulatory framework first proposed by Leventhal and colleagues in the 1980s. Self-reported pain severity scores were captured using a Visual Analogue Scale (VAS). Emotional well-being was assessed using the Positive and Negative Affect Scale (PANAS). Associations were explored using Spearman’s Rank Correlation. Results 223 participants (64% female) completed the PPQ-YP. 38.2% of participants had a diagnosis of oligoarthritis, 29.6% had polyarthritis and equal proportions of participants had systemic, psoriatic or enthesitis related JIA (7.3%). Higher reported pain severity was significantly correlated with stronger beliefs about the greater impact of pain on life (rho=0.494, p &lt; 0.001), pain unpredictability (rho=0.369, p &lt; 0.001) and pain persistence (rho=0.278,p&lt;0.001). Higher pain controllability beliefs (that pain was controllable) were significantly associated with lower self-reported pain severity (rho=-0.526, p &lt; 0.001). Stronger beliefs about the impact of pain on life (rho=0.425,p=0.001) and pain coherence (poorer understanding about own pain: rho=-0.295,p=0.021) were significantly associated with more negative mood. Conclusion Pain beliefs (particularly about consequences, unpredictability, persistence and understanding) are linked to levels of pain severity and well-being in children with JIA. Adding to the evidence base on the link between pain catastrophising and illness outcomes, this research enhances our understanding of long-term illness and pain perceptions in young people through the implication of a wider range of pain beliefs and cognitions on illness outcomes. The PPQ-YP identified salient pain beliefs which should be considered in the design of potential interventions to improve pain outcomes in this group. Future research should aim to explore whether these perceptions can predict other important illness outcomes. Conflicts of Interest The authors declare no conflicts of interest.

Placebo analgesia induced by verbal suggestion in the context of experimentally induced fear and anxiety.

The role of state anxiety and state fear in placebo effects is still to be determined. We aimed to investigate the effect of fear of movement-related pain (FMRP) and contextual pain related anxiety (CPRA) on the magnitude of placebo analgesia induced by verbal suggestion. Fifty-six female participants completed a modified voluntary joystick movement paradigm (VJMP) where half participated in a predictable pain condition (PC), in which one of the joystick movements is always followed by pain and the other movement is never followed by pain, and half in an unpredictable pain condition (UC), in which pain was delivered unpredictably. By varying the level of pain predictability, FMRP and CPRA were induced in PC and UC respectively. Colour stimuli were presented at the beginning of each trail. Half of the participants were verbally informed that the green or red colour indicated less painful stimuli (experimental groups), the other half did not receive any suggestion (control groups). We measured self-reported pain intensity, expectancy of pain intensity (PC only), pain related fear and anxiety (eyeblink startle response and self-ratings) and avoidance behaviour (movement-onset latency and duration). The results indicate that the placebo effect was successfully induced in both experimental conditions. In the PC, the placebo effect was predicted by expectancy. Despite the fact that FMRP and CPRA were successfully induced, no difference was found in the magnitude of the placebo effect between PC and UC. Concluding, we did not find a divergent effect of fear and anxiety on placebo analgesia.