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. Figure 1 Figure 1. Disclosures Shah: 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.

Identifying pain trajectories in children and youth with cerebral palsy: a pilot study

Background Although chronic pain is common in children with cerebral palsy (CP), little is known about short-term pain fluctuations and their impact on children’s well-being. High-quality cohort studies are needed to understand the clinical course of pain in this population. We aimed to determine the feasibility of conducting a multicentre cohort study. In this pilot study we assessed: 1) study processes, 2) resource and 3) management indicators including recruitment and follow-up rates, data completeness, participant characteristics, and successes and barriers in the study conduct. Methods A multi-centre pilot cohort study was conducted with 10 Canadian children/youth with CP attending one of two children’s rehabilitation centers. We collected self-reported pain intensity (Faces Pain Scale-Revised [FPS-R], Numeric Rating Scale [NRS]); pain interference (PROMIS PI); pain location (pain diagram); physical and psychological well-being (KIDSCREEN-27), sleep characteristics, preceding months’ interventions, and some clinical characteristics at baseline. Average pain intensity was reported weekly for five weeks. Well-being, sleep and interventions were measured at baseline and again at five weeks. We used feasibility indicators to evaluate:1) study processes (e.g. recruitment, attrition rates); 2) resources (e.g. data completion, budgetary challenges); and 3) management (e.g. data optimization, variability of participants and pain scores). Results Between March and May 2019, 24 children and their parents/guardians were contacted and 20 met eligibility criteria. Of those, 10 agreed to in-person screening (50%) and were subsequently enrolled. The follow-up rate was 90% and self-reported missing data was minimal. Ninety percent of participants chose e-questionnaire follow-ups versus mailed paper questionnaires. Sixty percent required reminders to complete e-follow-ups. Participants were aged 8-17 years, five were female, GMFCS levels I-IV (none with level V), 90% had spastic CP and 80% reported having pain in the preceding week. Pain intensity (FPS-R) between participants ranged from 0-8/10 at baseline and 0-6/10 across all four weekly follow-ups. Conclusions This pilot study demonstrates the feasibility of conducting a multicentre cohort study to identify short-term pain trajectories and measure their association with well-being in children and youth with CP. Additional strategies to improve recruitment and accessibility for those with GMFCS levels V should be implemented in future studies.

Pain trajectories and possible predictors of a favourable course of low back pain in patients consulting musculoskeletal physicians in The Netherlands

Background In The Netherlands, low back pain patients can consult physicians specialized in musculoskeletal (MSK) medicine. Previous studies have reported on the characteristics of patients consulting MSK physicians, and the treatment options used. There are no studies yet reporting on the course of Low Back Pain (LBP) after treatment by musculoskeletal (MSK) physicians in The Netherlands. Methods In an observational cohort study MSK physicians recorded data about all low back pain patients presenting for a first consultation. At baseline they recorded age, gender, type and duration of the main complaint, and concomitant complaints. At the end of treatment they recorded the type of treatment and the number of treatment sessions. Patients were recruited to answer questionnaires at baseline, and at 6-weekly intervals during a follow-up period of six months. Patient questionnaires included information about previous medical consumption, together with PROMs measuring the level of pain and functional status. Latent Class Growth Analysis (LCGA) was used to classify patients into different groups according to their pain trajectories. Baseline variables were evaluated as predictors of a favourable trajectory using logistic regression analyses, and treatment variables were evaluated as possible confounders. Results A total of 1377 patients were recruited, of whom 1117 patients (81%) answered at least one follow-up measurement. LCGA identified three groups of patients with distinct pain trajectories. A first group (N = 226) with high pain levels showed no improvement, a second group (N = 578) with high pain levels showed strong improvement, and a third group (N = 313) with mild pain levels showed moderate improvement. The two groups of patients presenting with high baseline pain scores were compared, and a multivariable model was constructed with possible predictors of a favourable course. Male gender, previous specialist visit, previous pain clinic visit, having work, a shorter duration of the current episode, and a longer time since the complaints first started were predictors of a favourable course. The multivariable model showed a moderate area under the curve (0.68) and a low explained variance (0.09). Conclusions In low back pain patients treated by musculoskeletal physicians in The Netherlands three different pain trajectories were identified. Baseline variables were of limited value in predicting a favourable course.

Trajectories of Pain After Cardiac Surgery: Implications for Measurement, Reporting, and Individualized Treatment

Background: Postoperative pain after cardiac surgery is a significant problem, but studies often report pain value as an average of the study cohort, obscuring clinically meaningful differences in pain trajectories. We sought to characterize heterogeneity in postoperative pain experiences. Methods: We enrolled patients undergoing a cardiac surgery at a tertiary care center between January 2019 and February 2020. Participants received an electronically-delivered questionnaire every 3 days for 30 days to assess incision site pain level. We evaluated the variability in pain trajectories over 30 days by the cohort-level mean with confidence band and latent classes identified by group-based trajectory model. Group-based trajectory model estimated the probability of belonging to a specific trajectory of pain. Results: Of 92 patients enrolled, 75 provided ≥3 questionnaire responses. The cohort-level mean showed a gradual and consistent decline in the mean pain level, but the confidence bands covered most of the pain score range. The individual-level trajectories varied substantially across patients. Group-based trajectory model identified 4 pain trajectories: persistently low (n=9, 12%), moderate declining (initially mid-level, followed by decline; n=26, 35%), high declining (initially high-level, followed by decline; n=33, 44%), and persistently high pain (n=7, 9%). Persistently high pain and high declining groups did not seem to be clearly distinguishable until approximately postoperative day 10. Patients in persistently low pain trajectory class had a numerically lower median age than the other 3 classes and were below the lower confidence band of the cohort-level approach. Patients in the persistently high pain trajectory class had a longer median length of hospital stay than the other 3 classes and were often higher than the upper confidence band of the cohort-level approach. Conclusions: We identified 4 trajectories of postoperative pain that were not evident from a cohort-level mean, which has been a common way of reporting pain level. This study provides key information about the patient experience and indicates the need to understand variation among sites and surgeons and to investigate determinants of different experience and interventions to mitigate persistently high pain.

OP0196 CIRCULATING LEVEL OF IL-6 IS ASSOCIATED WITH 10.7-YEAR KNEE CARTILAGE VOLUME LOSS AND WORSE PAIN TRAJECTORY

Background:There is growing evidence that inflammation plays a critical role in osteoarthritis (OA) progression and its symptoms evolution. OA pain is heterogeneous and there are distinct subgroups within OA pain patients. Recently, we identified three homogeneous subgroups following distinct pain trajectories in which metabolic mechanism may be involved. Whether circulating inflammatory markers are associated with long-term knee structural changes on MRI, and whether the association between inflammatory markers and the trajectories we identified differs remain to be clarified.Objectives:To examine whether inflammatory markers are associated with 10.7-year knee structural changes including knee cartilage volume (CV) and bone marrow lesions (BMLs), and to assess the associations between inflammatory markers and different pain trajectories.Methods:This study was conducted as part of a population-based older adult (mean age 63 years, 51% of females) cohort study with 1,099, 875, 768 and 563 participants attending at baseline, and 2.6-, 5.1- and 10.7-year follow-ups. Circulating levels of interleukin (IL)-6, tumour necrosis factor alpha (TNF-α) and high sensitivity C-reactive protein (CRP) were measured at baseline in 193 randomly selected participants. T1-weighted or T2-weighted MRI of the right knee was performed to measure CV and BMLs at baseline and 10.7-year. X-ray was performed to assess radiographic knee osteoarthritis (ROA). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain questionnaire was used to measure knee pain at all four visits. Data on demographic, psychological, lifestyle and comorbidities were also collected. Pain trajectories was previously identified using the group-based trajectory modelling. Linear, log-binomial and multi-nominal logistic regression modellings were used for the analyses.Results:IL-6 was associated with both medial and lateral tibial CV loss (Medial: β=-0.51% per log pg/ml, 95%CI -0.88 to -0.15; Lateral: β=-0.34% per log pg/ml, 95%CI -0.64 to -0.04) after adjusting for age, sex, body mass index, physical activity, comorbidities, and ROA. TNF-α was not associated with either medial or lateral CV loss, but CRP was positively associated with medial tibial CV loss (Medial: β=0.27% per log mg/L, 95%CI 0.04 to 0.49), not lateral CV loss. No inflammatory markers were found to associate with medial and lateral BML size increase. Of 169 participants who had complete data at baseline, 54%, 35% and 11% of participants fell into ‘Minimal pain’, ‘Mild pain’ and ‘Moderate pain’ trajectory group, respectively. In multivariable analysis, IL-6 was associated with an increased risk of being a ‘Moderate pain’ trajectory (relative risk ratio [RRR]: 4.03, 95%CI 1.34 to 12.13) in comparison with ‘Minimal pain’ trajectory group. There was no significant association of TNF-α and CRP with trajectory groups.Conclusion:IL-6 was associated with both medial and lateral tibial CV loss (Medial: β=-0.51% per log ml/pg, 95%CI -0.88 to -0.15; Lateral: β=-0.34% per log ml/pg, 95%CI -0.64 to -0.04) after adjusting for age, sex, body mass index, physical activity, comorbidities, and ROA. TNF-α was not associated with either medial or lateral CV loss, but CRP was positively associated with medial tibial CV loss (Medial: β=0.27% per log ml/pg, 95%CI 0.04 to 0.49), not lateral CV loss. No inflammatory markers were found to associate with medial and lateral BML size increase. Of 169 participants who had complete data at baseline, 54%, 35% and 11% of participants fell into ‘Minimal pain’, ‘Mild pain’ and ‘Moderate pain’ trajectory group, respectively. In multivariable analysis, IL-6 was associated with an increased risk of being a ‘Moderate pain’ trajectory (relative risk ratio [RRR]: 4.03, 95%CI 1.34 to 12.13) in comparison with ‘Minimal pain’ trajectory group. There was no significant association of TNF-α and CRP with trajectory groups.Disclosure of Interests:None declared